The mammary gland: A unique organ for the study of development and tumorigenesis

  • Daniel Medina


The microanatomy and development of the mammary gland are unique and a reflection of its function to synthesize and deliver milk to the newborn offspring. The uniqueness of the mammary gland resides in several factors. First, the mammary parenchyma undergoes the vast majority of its growth postpubertally, thus enabling experiments on development to be performed in the juvenile or adult and presenting opportunities for experimental manipulation of the gland not available with other organs. On the basis of this characteristic, the fat pad transplantation method was developed, which resulted in the elaboration of important concepts in senescence, immortalization, and preneoplasia. Second, the accessibility of the gland and the ductal organization allows delivery and localization of specific molecules to mammary parenchyma cells, the cells which are the site of origin of neoplastic development. Third, the organ is the target of viral, chemical, and physical carcinogens, allowing development of unique and complex models for neoplastic development. Finally, the complexity of hormone and growth factor regulation of mammary gland function allows a sophisticated approach to the study of hormone action. The purpose of this review is to illustrate some unique properties of the gland which provide the basis for specialized approaches to developmental, neoplastic, and functional problems.

Key words

Mammary gland development transplantation 


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  1. 1.
    A. Cooper (1845).The Anatomy and Diseases of the Breast Lea and Blanchard, Philadelphia.Google Scholar
  2. 2.
    K. Kratochwil (1987). Epithelium-mesenchyme interactions in the fetal mammary gland. In D. Medina, W. Kidwell, G. Heppner, and E. Anderson (eds.),Cellular and Molecular Biology of Mammary Cancer Plenum Press, New York, pp. 67–80.Google Scholar
  3. 3.
    T. Sakakura (1991). New aspects of stroma-parenchyma relations in mammary gland differentiation.Int. Rev. Cytol. 125165–202.PubMedGoogle Scholar
  4. 4.
    C. Q. Lin and M. J. Bissell (1993). Multi-faceted regulation of cell differentiation by extracellular matrix.FASEB J. 7737–743.PubMedGoogle Scholar
  5. 5.
    W. Imagawa, J. Yang, R. Guzman, and S. Nandi (1994). Control of mammary gland development. In E. Knobil and J. D. Neill (eds.),The Physiology of Reproduction, Vol. 2, 2nd ed., Raven Press, New York, pp. 1033–1065.Google Scholar
  6. 6.
    J. M. Williams and C. W. Daniel (1983). Mammary ductal elongation: Differentiation of myoepithelium and basal lamina during branching morphogenesis.Dev. Biol. 97274–290.CrossRefPubMedGoogle Scholar
  7. 7.
    J. Russo, B. A. Gusterson, A. E. Rogers, I. H. Russo, S. R. Wellings, and M. J. Zwieten (1990). Comparative study in human and rat mammary tumorigenesis.Lab. Invest. 62244–278.PubMedGoogle Scholar
  8. 8.
    R. E. Munford (1963). Changes in the mammary glands of rats and mice during pregnancy, lactation and involution.J. Endocrinol. 281–44.PubMedGoogle Scholar
  9. 9.
    L. J. Faulkin, Jr. and K. B. DeOme (1960). Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse.J. Natl. Cancer Inst. 24953–969.PubMedGoogle Scholar
  10. 10.
    Y. Friedmann, C. A. Daniel, P. Strickland, and C. W. Daniel (1994).Hox genes in normal and neoplastic mouse mammary gland.Cancer Res. 545981–5985.PubMedGoogle Scholar
  11. 11.
    K. B. DeOme, L. J. Faulkin, Jr., H. A. Bern, and P. E. Blair (1959). Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice.Cancer Res. 19515–520.PubMedGoogle Scholar
  12. 12.
    D. Medina (1982). Mammary tumors. In H. L. Foster, J. D. Small, and J. G. Fox (eds.),The Mouse in Biomedical Research, Vol. IV, Academic Press, New York, pp. 373–396.Google Scholar
  13. 13.
    D. Medina (1979). Serial transplantation of chemical carcinogen-induced mouse mammary ductal dysplasias.J. Natl. Cancer Inst. 62397–405.PubMedGoogle Scholar
  14. 14.
    C. W. Daniel (1972). Aging in cells during serial propagationin vivo.Adv. Gerontol. Res. 4167–200.Google Scholar
  15. 15.
    E. M. Rivera and S. Vijayaraghavan (1982). Proliferation of ductal outgrowths by carcinogen-induced rat mammary tumors in gland-free mammary fat pads.J. Natl. Cancer Inst. 69517–525.PubMedGoogle Scholar
  16. 16.
    B. Alston-Mills and E. M. Rivera (1985). Factors influencing the differential growth of rat mammary tumor fragments and cells transplanted in gland-free and gland-containing mammary fat pads.Eur. J. Cancer Clin. Oncol. 101233–1243.CrossRefGoogle Scholar
  17. 17.
    S. P. Ethier and K. C. Cundiff (1987). Importance of extended growth potential and growth factor independence onin vivo neoplastic potential of primary rat mammary carcinoma cells.Cancer Res. 475316–5322.PubMedGoogle Scholar
  18. 18.
    K. H. Clifton and M. N. Gould (1985). Clonagen transplantation assay of mammary and thyroid epithelial cells. In C. S. Potten and J. H. Hendry (eds.),Cell Clones Churchill Livingstone, New York, pp. 128–138.Google Scholar
  19. 19.
    E. C. Kordon, R. A. McKnight, C. Jhappan, L. Henninghausen, G. Merlino, and G. H. Smith (1995). Ectopic TGFβ1 expression in the secretory mammary epithelium induces early senescence of the epithelial stem cell population.Dev. Biol. (in press).Google Scholar
  20. 20.
    D. W. Morris and R. D. Cardiff (1987). The multistep model of mouse mammary tumor development.Adv. Viral Oncol. 7123–140.Google Scholar
  21. 21.
    K. Hoshino (1978). Mammary transplantation and its histogenesis in mice. In A. Yokoyama, H. Mizuno, and H. Nagasawa (eds.),Physiology of Mammary Glands. University Park Press, Baltimore, pp. 163–228.Google Scholar
  22. 22.
    C. W. Daniel, G. B. Silberstein, K. VanHorn, P. Strickland, and S. Robinson (1989). TGF-β1-induced inhibition of mouse mammary ductal outgrowth: Developmental specificity and characterization.Dev. Biol. 13520–30.CrossRefPubMedGoogle Scholar
  23. 23.
    W. Jones, R. C. Hallowes, N. Choongkittaworn, H. L. Hosick, and R. Dils (1983). Isolation of the epithelial subcomponents of the mouse mammary gland for tissue-level culture studies.J. Tissue Culture Meth. 817–25.CrossRefGoogle Scholar
  24. 24.
    S. R. Dundas, M. G. Ormerod, B. A. Gusterson, and M. J. O'Hare (1991). Characterization of luminal and basal cells flow-sorted from the adult rat mammary parenchyma.J. Cell Sci. 100459–471.PubMedGoogle Scholar
  25. 25.
    D. Medina, F. Shepherd, and T. Gropp (1978). Enhancement of the tumorigenicity of preneoplastic mammary nodule lines by enzymatic dissociation.J. Natl. Cancer Inst. 601121–1126.PubMedGoogle Scholar
  26. 26.
    T. K. Bera, R. C. Guzman, S. Miyamoto, D. K. Panda, M. Sasaki, K. Hanyu, J. Enami, and S. Nandi (1994). Identification of a mammary transforming gene (MAT1) associated with mouse mammary carcinogenesis.Proc. Natl. Acad. Sci. USA 919789–9793.PubMedGoogle Scholar
  27. 27.
    B. Wang, W. S. Kennan, J. Yasukawa-Barnes, M. J. Lindstrom, and M. N. Gould (1991). Carcinoma induction following directin situ transfer of v-Ha-ras into rat mammary epithelial cells using replication-defective retrovirus vectors.Cancer Res. 512642–2648.PubMedGoogle Scholar
  28. 28.
    S. Coleman and C. W. Daniel (1990). Inhibition of mouse mammary ductal morphogenesis and down-regulation of the EGF receptor by epidermal growth factor.Dev. Biol. 137425–433.CrossRefPubMedGoogle Scholar
  29. 29.
    S. R. Wellings, M. M. Jensen, and R. G. Marteum (1975). An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.J. Natl. Cancer Inst. 55231–274.PubMedGoogle Scholar
  30. 30.
    C. W. Welsch, D. H. O'Connor, C. F. Aylsworth, and L. G. Sheffield (1987). Normal but not carcinomatous primary rat mammary epithelium readily transplanted to and maintained in the athymic nude mouse.J. Natl. Cancer Inst. 78557–565.PubMedGoogle Scholar
  31. 31.
    R. R. Mehta, J. M. Graves, G. D. Hart, A. Shilkaites, and T. K. Das Gupta (1993). Growth and metastasis of human breast carcinomas with Matrigel in athymic mice.Breast Cancer Res. Treat. 2565–71.CrossRefPubMedGoogle Scholar
  32. 32.
    L. Henninghausen (1990). The mammary gland as a bioreactor; production of foreign proteins in milk.Protein Expression Purific. 13–8.CrossRefGoogle Scholar
  33. 33.
    P. A. W. Edwards, C. L. Abram, and J. M. Bradbury, Genetic manipulation of mammary epithelium by transplantation.J. Mammary gland Biol. Neoplasia, this issue.Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Daniel Medina
    • 1
  1. 1.Department of Cell BiologyBaylor College of MedicineHouston

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